Predictive value of placental real-time shear wave elastography combined with 3-dimensional power Doppler index for preeclampsia

This study aimed to investigate the value of placental real-time shear wave elastography combined with three-dimensional power Doppler index (3D-PDI) in the prediction of preeclampsia. We conducted a retrospective study selecting 60 pregnant women diagnosed with preeclampsia as the experimental group and 60 normal pregnant women as the control group from January 2021 to December 2022. The elastic modulus values of different regions of the placenta and placental 3D-PDI were detected and compared between the two groups. The ROC curve was used to evaluate the diagnostic value of each parameter, alone or in combination, for preeclampsia. The study findings demonstrated that the elastic modulus values of different regions of the placenta and 3D-PDI of the two groups have statistical significance. The values of SWE, VI, FI, and VFI are different in prediction of preeclampsia, and the combination of various parameters can improve the prediction value. Overall, our study provides a valuable method for the prediction of preeclampsia with the advantages of non-invasiveness, efficiency, and simplicity.


Introduction
Preeclampsia (PE) is a unique complication of women during pregnancy, which refers to high blood pressure that develops after 20 weeks of pregnancy with proteinuria or without proteinuria but with new onset of any of the following: thrombocytopenia, renal insufficiency, impaired liver function, pulmonary edema, or headache unresponsive to medication. [1,2]Besides, PE can cause headache, dizziness, nausea, vomiting, epigastric discomfort, and other symptoms.PE is the leading cause of maternal morbidity and mortality worldwide with the incidence of 3% to 8%. [3]Until now, the pathogenesis of PE is not clear.It is believed that the failure of uterine spiral artery recasting causes placental ischemia and hypoxia dysplasia, a variety of placental factors entering the maternal blood leads to systemic inflammatory response and vascular endothelial damage, and finally, PE is developed. [4]t has also been suggested that placental stiffness increases in patients with PE for the following reasons: The mechanisms for increased placental stiffness in PE may be that trophoblast invasion of the maternal spiral arteries is impaired, resulting in reduced placental perfusion and in a hypoxic placental milieu.Hypoxia arouses collagen and fibrin deposition and fibrosis, which together leads to increased placental stiffness. [2,5,6]Postpartum PE patients can return to normal, so the abnormality of the placenta plays a very important role in the occurrence of PE.Therefore, placental monitoring is of great significance to understand fetal growth and development and take effective clinical treatment in a timely manner. [7]The diagnosis of PE in the past requires the detection of blood pressure, urine protein, and clinical symptoms of the patient, but not all pregnant women can be tested for the above relevant indicators in time, so that they are only found when they have serious complications, which seriously affects the health of the mother and fetus.At present, there are few indicators that can predict PE, and there is a lack of effective predictors in the first trimester.In particular, there is a lack of effective joint predictors.10] Women with hypertensive disorders of pregnancy have increased shear wave elastography (SWE) of the placenta Informed consent was obtained from all individual participants included in the study.
The datasets generated during and/or analyzed during the current study are publicly available.

Tian et al. • Medicine (2024) 103:10
Medicine compared with the placentas of women with uneventful pregnancies. [11]Therefore, we aimed to evaluate the tissue stiffness of the placenta and the placental blood perfusion, respectively, to evaluate the predictive value of these 2 parameters for PE, alone or in combination.

Research subjects
From January 2021 to December 2022, 60 pregnant women who were treated in our hospital and diagnosed with PE were selected as the experimental group, and 60 normal pregnant women in the same period were selected as the control group.All participants were singletons, without fetal malformations, uterine malformations, underlying medical conditions, and other pregnancy comorbidities.All maternal placentas were located on the anterior wall of the uterus and can be fully and clearly monitored, which is helpful to ensure the accuracy of the measurement.PE diagnostic criteria are as follows: systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or more on 2 occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure; systolic blood pressure of 160 mm Hg or more or diastolic blood pressure of 110 mm Hg or more.
(Severe hypertension can be confirmed within a short interval [minutes] to facilitate timely antihypertensive therapy.)Proteinuria 300 mg or more per 24 hours of urine collection (or this amount extrapolated from a timed collection) or protein/creatinine ratio of 0.3 mg/dL or more or Dipstick reading of 2+ (used only if other quantitative methods not available).
Or in the absence of proteinuria, new-onset hypertension with the new onset of any of the following: thrombocytopenia: platelet count less than 100,000 × 10 9 /L; renal insufficiency: serum creatinine concentrations greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease; impaired liver function: elevated blood concentrations of liver transaminases to twice normal concentration; pulmonary edema; new-onset headache unresponsive to medication and not accounted for by alternative diagnoses or visual symptoms. [1]The age, height, weight, gestational age, reproductive history, and history of PE of all study participants were recorded to calculate the body mass index (BMI).This experiment has been approved by the Research Ethics Committee of Binzhou Medical University Hospital, and all study subjects received informed consent (Ethics approval number: 2023-LW-69).

Detection of placental elasticity. Sonologist Aixplorer
V color Doppler ultrasound diagnostic instrument was equipped with convex array probe (frequency 3.5-5.0MHz) and SWE quantitative analysis system.The pregnant woman lay on her back.Routine ultrasound examination determines the center and edge of the placenta.The probe was gently placed vertically and fixed at the scanning site.The pregnant woman was instructed to breathe calmly.Fetal movements and uterine contractions were avoided.Placental umbilical cord insertion point and obvious calcification and blood sinus were avoided.
In elastography mode, when the image is stable, the quantitative analysis system was performed.The SWE value was obtained with the diameter of the sampling frame at 5 mm and the sampling depth was controlled within 8 cm.The average value of 3 measurements with 3-to 5-second intervals was calculated for each region of interest (Fig. 1).VOCAL software was used to obtain the placenta threedimensional power Doppler index (3D-PDI): VI, FI, VFI.All data collected in this study were performed by an experienced prenatal diagnostic sonographer (Fig. 2).

Statistical analysis
Using SPSS 26.0 statistical software, the measurement data are expressed as mean ± standard deviation (x̄ ± s), and the mean comparison of the 2 samples is measured by the t-test of 2 independent samples, and the counting data are expressed in n (%), using the χ 2 test.The ROC was used to evaluate the predictive value of each parameter, alone or in combination, for PE, and to calculate the incidence of PE at a false-positive rate of 5%.P < .05 is statistically significant.

Comparison of general data of pregnant women in the experimental and control group
There was no significant difference in age, gestational age, BMI, history of PE, and history of menstrual labor between the 2 groups (all P > .05;Table 1).

Comparison of placenta SWE values of pregnant women in experimental and control group
The SWE values of central fetal face, central maternal surface, marginal fetal surface, and marginal maternal surface of placenta in the experimental group were higher than those in the control group, and the differences were statistically significant (all P < .05).However, there was no difference in SWE values in different regions of the placenta in each group (all P > .05;Table 2).

Comparison of placenta 3D-PDI of pregnant women in experimental and control group
The placenta VI, FI, and VFI of the experimental group were lower than those in the control group, and the differences were statistically significant (all P < .05;Table 3).

Relationship between PE and maternal placental SWE value and 3D-PDI alone or in combination
The ROC was plotted, and the area under the ROC was calculated to compare the sensitivity and specificity of SWE, VI, FI, and VFI in predicting PE.The ROCs show that all of SWE, VI, FI, and VFI have predictive value for PE (all P < .05).When the false-positive rate is 5%, the sensitivity of SWE, VI, FI, and VFI is 0.800, 0.850, 0.850, and 0.800, respectively (Fig. 3).
The parameters were jointly combined to plot ROCs, and the SWE combined VI, FI, VFI and the combination of the 4 had high predictive value (all P < .05),and when the falsepositive rate was 5%, the combined diagnostic sensitivity was 0.750, 0.800, 0.850, and 0.833, respectively (Table 4 and Fig. 4).

Discussion
SWE is mainly used to evaluate the hardness of lesions.SWE has been widely used in the diagnosis of breast, thyroid, liver, and other organs, as it not only avoids the subjective influence of the operator and comparison with surrounding tissues but also has the advantages of noninvasion and good repeatability. [1]The use of SWE technology in obstetrics is still relatively rare, but it has been reported that elastography is safe for pregnant women. [12]hree-dimensional power color Doppler ultrasound is a noninvasive ultrasound technique developed from conventional ultrasound to clearly show blood perfusion. [13]It is not affected by the detection angle and is sensitive to low-speed blood flow and tiny blood vessels in the placenta. [14]The reconstruction image is more intuitive and can be analyzed offline by VOCAL software to obtain VI, FI, VFI (VI represents the number of blood vessels in the area of interest; FI stands for area of interest blood flow strength; VFI is a comprehensive evaluation index representing the sum of blood vessels and blood flow), thereby quantitatively evaluating the number of vessels and blood flow rate of placental tissue. [15]In this study, the combination of these 2 techniques was applied to evaluate placental function more comprehensively, meanwhile, the limitations and drawbacks of previous evaluation methods such as placental grading and color Doppler can be avoided.
There was no difference in the general information of pregnant women in experimental and control group, such as age, gestational age, BMI, etc, which avoids the interference of other factors other than PE on the study results.][18] That is to say the selection of the region of interest for placental elasticity measurement does not affect the elastic value.[21][22] Traditional 2-dimensional ultrasound can only grade the placenta, provide placental morphological characteristics.It is interfered by many subjective factors, while SWE can objectively and quantitatively reflect the change of placental tissue hardness, and indirectly reflect the functional state of the placenta in patients with PE.The results of this study also suggest that the placental 3D-PDI VI, FI, and VFI of PE patients are lower than that of normal pregnant women in the control group.It is because that the blood pressure of pregnant women with PE is increased, and the placental circulatory pressure increases, resulting in irreversible embolism, stenosis, degeneration, necrosis, and other conditions in placental blood vessels, which usually worsen with the exacerbation of the disease. [23,24]Compared with color Doppler ultrasound, 3-dimensional power Doppler can more clearly demonstrate  the microvascular and low-speed blood flow in the placenta, quantitatively evaluate the thinning and quantity of blood vessels in the placenta, and is not affected by scanning angle, vascular aliasing, blood flow velocity, etc.It can more clearly demonstrate the placental blood perfusion status to determine whether there is ischemia and the degree of ischemia in the placenta in patients with PE.
By ROC analysis, we found that placental SWE, 3D-PDI VI, FI, and VFI all have the value in prediction of PE, and the area under the ROC was 0.769, 0.779, 0.754, and 0.817, respectively.In this study, we further evaluated whether the combination of multiple parameters could improve the    predictive value for PE.The results showed that the area under the ROC of SWE values combined with VI, FI, or VFI, or the combination of the 4 were 0.846, 0.861, and 0.916, respectively, which were higher than the predicted values of each parameter alone.This indicates that placental SWE, VI, FI, and VFI are helpful in predicting PE, and that the combination of multiple parameters can improve the prediction efficiency.

Conclusion
In conclusion, the results show that the placental elastic modulus value, 3D-PDI VI, FI, and VFI have different levels of predictive value for PE, and the combined detection of various parameters can improve the prediction value, and the combined prediction value of 4 parameters is the highest.SWE and 3D-PDI, as a noninvasive diagnostic method, can be used as an important means to detect placental function in patients with PE by detecting placental hardness and blood perfusion, and provide an objective basis for clinical diagnosis.
The shortcomings of this study are the lack of placental pathology examination information as a control, and there is no group discussion of the severity of PE.The elasticity measurement is limited by depth, and it is impossible to detect the elasticity of posterior wall and lateral wall placenta, which will also be the focus of our future research.We will also conduct a multi-center study, collect data from different research centers, and further explore the predictive value of placental elasticity and 3D-PDI alone or in combination for PE.

Figure 2 .
Figure 2. Detection of placental 3-dimensional power Doppler index.(A) Volumetric data acquisition; (B) Three-dimensional image of placental blood vessels; (C) VOCAL software quantitative analysis.VOCAL = virtual organ computer-aided analysis.
VOCAL) software.During the examination, the pregnant woman was instructed to breathe calmly.Fetal movements were avoided.The entrance of the umbilical cord of the placenta was selected for measurement in the 3-dimensional energy Doppler vascular mode.All placental thickness tissue were enveloped, and the volume data were collected quickly.

Table 1
Comparison of general information on pregnant women in the 2 groups.

Table 2
Comparison of placental elastic modulus values in different regions of the 2 groups (x̄ ± s).Case number Central fetal surface Central maternal surface Marginal fetal surface Marginal maternal surface Average value

Table 3
Comparison of three-dimensional power Doppler indices of 2 groups of placenta (x̄ ± s).

Table 4
Combined detection of area under the ROC of preeclampsia.